| Type 2 diabetes mellitus is a multi-source metabolic disease characterized by absolute or relative lack of insulin secretion and insulin resistance(IR).Gamma-aminobutyric acid(GABA)is an important neural inhibition in mammals.It can slow down oxidative stress,protect islet β cells and regulate blood glucose level of animals.Pancreas and muscle are important tissues which regulate the balance of insulin and blood glucose in the development of diabetes.GABA can protect the pancreas and muscle in the high-glucose injury model were showed in vitro experiments but its specific mechanism still needs to be further studied.This article aims to investigate the role of improving pancreatic injury and insulin resistance of GABA in type 2 diabetic rats and its possible mechanism.Eighty Wistar male rats were randomly divided into 5 groups: normal control group(C),T2 DM model group(C+)by high-fat diet combined with intraperitoneal dexamethasone(DEX),0.045 g/kg BW GABA feed+T2DM Group(T1),0.090 g/kg BW GABA feed+T2DM group(T2)and 0.150 g/kg BW GABA feed+T2DM group(T3).After the completion of the model,compared with the C group,the blood glucose and insulin levels in the C+ group were significantly abnormal,which indicated the success of the T2 DM model.Moreover,compared with C+ group,AUC and HOMA-IR of the T group were significantly lower and plasma triglyceride(TG),total cholesterol(TC),and high-density lipoprotein cholesterol(HDL-C)levels were significantly reduced;The content of malondialdehyde(MDA)and reactive oxygen species(ROS)in the plasma,liver,and muscle were decreased obviously and the total antioxidant capacity and enzyme activity increased significantly.The results showed that GABA diet intervention can increase the body’s GABA content,significantly improve the abnormal glucose tolerance and insulin levels in type 2 diabetic rats,and reduce the body’s oxidative stress response.The expressions of glutamic acid decarboxylase GAD65,GAD67 in the pancreas were significantly upregulated;the mRNA expression of Nrf2,Bax,MafA and PDX-1 genes related to apoptosis and insulin secretion in pancreas were remarkably up-regulated in group T,and the expression of apoptosis-related genes GSK-3β,Bcl-2 and casepase-3 were significantly increased;the expression levels of PI3 K,Akt,and Nrf2 genes in the pancreas were significantly upregulated,and the expression of GSK-3β was significantly down-regulated.This indicates that GABA activates the GSK-3β/Nrf-2 pathway to a certain degree to protect pancreatic tissue,reduce islet β-cell damage,and promote insulin secretion.In muscle,mRNA expression of insulin-related genes AMPK,IRS-1,InsR-1,GLUT4 were significantly up-regulated,and the expression of glucocorticoid receptor gene GR was significantly down-regulated,the expression of PI3 K and Akt were significantly up-regulated in muscle synthesis-related pathway genes,and the expression of FOXO1,MAFbx,and MuRF1 genes related to muscle breakdown were significantly down-regulated.Compared with C group,insulin resistance-related pathway gene mTOR and S6K1 C+ group were compensatory increased.Compared with C+ group,the expression of these two genes in the T group was significantly reduced,and the expression of m TORC1 was significantly decreased,the expression of mTORC2 was significantly increased.Western bolt results showed that the expression of GSK-3β protein in the pancreas of T the T group was significantly decreased,and Nrf2 protein expression was significantly up-regulated;PI3K protein expression and AKT phosphorylation were significantly up-regulated and mTOR protein expression was significantly decreased in muscles.These results indicate GABA diet can increase muscle sensitivity to insulin by affecting the mTOR/S6K1/IRS-1 pathway in muscle tissue,and improve muscle catabolic responses to relieve muscle atrophy,which in turn eases Insulin resistance symptoms in T2 DM patients.Most of these results were most pronounced in the T2 group. |
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